A coordinated multidisciplinary approach is planned to study the teratogenic effects of cholinergic insecticides on chick and quail embryos and mammalian cells. We found that both the cholinergic- and NAD-linked mechanisms are still very much involved in the insecticide-induced teratology and that the very young chick embryos (days 1-3) are the most susceptible to the insecticides. Our plan is to study: insecticide effects on the developing cervical vertebrae of the chick embryos; the cellular mechanisms of the wry neck syndrome and the undulating notochord; insecticide effects on the chick and mammalian embryo, in vitro; insecticide effects on embryonic antigens of the developing chick embryo; the influence of insecticides on the migratory patterns of primitive stem cells; insecticides and other teratogens on cell differentiation, using in vitro models; by means of electron microscopy our hypothesis that these insecticides act at the cellular level in part by affecting the normal formation or functon of microfilaments, microtubules and the extracellular matrix; the relative toxicity (LD50) of a number of these insecticides to the young embryo; histologically, embryos injected with selected insecticides to determine the breadth of defects produced; how the cholinergic insecticides act to decrease the NAD content of early chick embryos; how the cholinergic insecticides affect some of the normal processes of NAD utilization in the early chick embryo; how the cholinergic insecticides affect certain differentiation processes in vitro and the possible role of poly(ADP-ribose) in them; and how the OP insecticides affect protein phosphorylation in chick limb bud mesenchymal cells, especially in the chromatin proteins of those cells.